It is necessary to identify agents which are capable of inhibiting carcinogenesis in the large bowel. Investigation into the mechanisms of colorectal carcinogenesis suggests that antioxidants may have such capability. Butylated hydroxyanisole (BHA) retards experimental large bowel carcinogenesis; ascorbic acid (AA) ingestion is associated with a reduction in number and size of adenomas in patients with multiple polyposis. Human consumption of both of these agents has proven to be well tolerated. Toxicity studies have not demonstrated significant problems. The proposed study is designed to demonstrate efficacy of AA and BHA given concurrently in chemoprevention of experimental large bowel cancer. The optimum dose of each agent is to be determined. Any advantage of oral (systemic) vs. rectal (local) administration will be determined. The superior agent will be determined. Effects of AA and BHA in combination will be studied. Toxicity will be documented. First, AA and/or BHA will be administered orally or rectally in varying dosage to CF1 mice that are being given the large bowel carcinogen, 1,2-dimethylhydrazine (DMH). After 40 weeks, survival, tumor incidence and histology, and toxicity will be determined. Next, the procedure will be repeated in mice being fed only the minimum amount of food consumed by any group in experiment 1 in order to relate any growth effect or toxicity to dietary intake vs. toxicity of the drugs. Third, the most effective dose of each agent and combination, as determined in experiment 1, will be administered to mice receiving DMH. Mice will be sacrificed at intervals to determine effect of AA and/or BHA on rate of development of large bowel neoplasm.